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Biomedical subjects

Stephan Zierz

Publications and source records attributed to Stephan Zierz.

At least 19 recordsLinked to original sources
PubMed2006

Between Wallenberg syndrome and hemimedullary lesion: Cestan-Chenais and Babinski-Nageotte syndromes in medullary infarctions.

In comparison with the lateral (Wallenberg), medial (Dejerine) and hemimedullary (Reinhold) medulla oblongata syndromes, the Babinski-Nageotte and Cestan-Chenais syndromes are much less familiar cerebrovascular disorders. While the Babinski-Nageotte syndrome is usually confused with the hemimedullary syndrome, reports of the extremely rare Cestan-Chenais syndrome are missing from the modern neurological literature. The pathological and magnetic resonance imaging (MRI) correlations of the Cestan-Chenais syndrome have not been shown so far. We compared clinical and MRI features of two patients exhibiting classical Babinski-Nageotte and Cestan-Chenais syndromes according to their original descriptions with those of three patients with lateral, medial and hemimedullary syndromes. Our study shows that Babinski-Nageotte syndrome includes all symptoms of the Wallenberg syndrome and additionally contralateral hemiparesis due to a spreading of the "Wallenbergian" lateral lesion to the pyramidal tract. The Cestan-Chenais syndrome includes all symptoms of the Babinski-Nageotte syndrome with the exception of the ipsilateral cerebellary hemiataxia because of sparing of the posterior spinocerebellar tract. The Babinski-Nageotte syndrome is neither clinically nor on MRI identical with hemimedullary syndrome. Hypoglossal palsy, an invariable symptom of hemimedullary lesion is not part of the Babinski-Nageotte syndrome. The contralateral hypesthesia is dissociated in the Babinski-Nageotte syndrome. The Babinski-Nageotte and Cestan-Chenais syndromes are intermediolateral medullary syndromes with all (Babinski-Nageotte) or nearly all (Cestan-Chenais) features of the lateral and some features of the medial medulla oblongata syndromes.

Adult↗
PubMed2006

Lactate production upon short-term non-ischemic forearm exercise in mitochondrial disorders and other myopathies.

BACKGROUND: The nonischemic forearm exercise test (NIFET) has been shown to be as effective as the classic ischemic forearm exercise test (IFET) in the diagnosis of patients with McArdle disease. Recently, the lactate increase normalized to the mechanical energy production in NIFET was suggested to have a intermediate sensitivity and satisfactory specifity for the screening of mitochondrial disorders. METHODS: NIFET at 80% maximal contraction force (MCF) was performed in normal controls (n = 41), patients with mitochondrial disorders (n = 15) and other myopathies (diseased controls, n = 20). 26 healthy volunteers also underwent IFET at 80% MCF. The ratio of lactate increase and workload was defined as specific lactate production (mmol x s/N x l). RESULTS: In normal controls there was no significant different lactate increase during NIFET and IFET. The workload performed showed only a weak significant positive correlation with the lactate increase in the NIFET in normal controls (r(2) = 0.20) but not in IFET and NIFET with patients. A moderate negative correlation of specific lactate production and the absolute workload was found in all groups and in both protocols (r(2) = 0.22-0.34). The specific lactate production was highest in patients with other myopathies, intermediate in patients with mitochondrial disorders and lowest in normal controls. NIFET showed a sensitivity of only 20 % and a specifity of 95% for normal controls, but only 75 % for diseased controls. CONCLUSION: The specific lactate production during NIFET is neither sufficiently specific nor sensitive for the diagnosis of mitochondrial disorders. Increased specific lactate production during rest-to-work transition period might be caused by increased acetyl group deficits.

Adolescent↗
PubMed2006

Lactate increase and oxygen desaturation in mitochondrial disorders--evaluation of two diagnostic screening protocols.

BACKGROUND: Mitochondrial disorders are characterized by an accumulation of lactate and an insufficient oxygen extraction from blood during exercise. Therefore, both parameters (lactate and oxygen saturation) can be used as screening tests in mitochondrial disorders. However, conflicting results regarding sensitivities and specifities of both tests have been reported. METHOD: We examined 27 patients with genetically defined mitochondrial disorders (single deletions n = 15, multiple deletions n = 5, A3243G mutation n = 7), patients with other neuromuscular disorders, and healthy controls. In the first test subjects performed intermittent isometric handgrip exercise (0.5 Hz) at 80% (3 minutes) and 30% (3 and 15 minutes) of maximal contraction force (MCF). Oxygen saturation and partial pressure in cubital venous blood from the exercising arm were measured. In the second test subjects underwent cycle ergometry at 30 W for 15 minutes. Venous lactate at rest, during and 15 minutes postexercise was determined. RESULT: Both tests showed specificities of 92-96%. Sensitivities for changes of venous oxygen partial pressure and oxygen saturation ranged from 21-26% at 80% MCF for 3 minutes to 47-58% at 30% MCF for 15 minutes. Sensitivities for venous resting, peak, and post-exercise lactate was 33%, 58%, and 67%, respectively. The degree of deoxygenation, however,was independent of the intensity and duration of the applied forces. Oxygen desaturation and lactate increase in patients with mitochondrial disorders were not different in patients with and without clinical symptoms of myopathy. There were significant correlations between the heteroplasmy and both the degree of oxygen desaturation and lactate increase in patients with single deletions. In patients who performed both protocols (n = 16) a combination of both tests increased sensitivity up to 87%. CONCLUSION: Oxygen desaturation in forearm exercise tests and lactate increase in cycle ergometry tests show a high specifity but only moderate sensitivity. Combination of the two screening test clearly increases the sensitivity.

Adolescent↗
PubMed2006

Novel mitochondrial transfer RNA(Phe) gene mutation associated with late-onset neuromuscular disease.

BACKGROUND: An extensive range of molecular defects have been identified in the human mitochondrial genome (mitochondrial DNA); many are associated with well-characterized, progressive neurological syndromes, but a minority of patients have uncharacteristic phenotypes in which symptoms may be relatively mild. OBJECTIVE: To describe a novel transfer RNA(Phe) mutation of mitochondrial DNA in a late-onset case with a mild phenotype of mitochondrial disease. DESIGN: Case report. PATIENT: A 66-year-old woman presented with a 4-year history of walking difficulties due to exercise intolerance and paresthesia in the feet. Clinical examination results were normal. Her deceased mother had similar walking difficulties, but her sister and 2 children were unaffected. RESULTS: The demonstration of a marked histochemical defect in cytochrome c oxidase activity on muscle biopsy prompted molecular investigation of mitochondrial DNA, revealing a novel maternally inherited mutation in the variable loop of the mitochondrial transfer RNA(Phe) gene. This 622G>A transition was heteroplasmic and segregated with cytochrome c oxidase deficiency in single fibers. CONCLUSION: This case serves to illustrate that primary defects of the mitochondrial genome should be considered even in older patients with late-onset, mild neuromuscular symptoms.

Age of Onset↗
PubMed2006

Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice.

OBJECTIVE: The aim of the present work was the detection of Mitochondrial dysfunction of Huntington's disease (HD). METHODS: We investigated muscle and muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type mice. RESULTS: Atrophic fibers, increased fuchsinophilic aggregates, and reduced cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements and Ca2+ accumulation experiments, a decreased stability of HD mitochondria against Ca2+-induced permeability transition was detected. Complex I-dependent respiration of HD mitochondria was more sensitive to inhibition by adding 10 microm Ca2+ than wild-type mitochondria. INTERPRETATION: Data suggest that the decreased stability of HD mitochondria against Ca2+ contributes to energetic depression and cell atrophy.

Animals↗
PubMed2006

Successful treatment of MuSK antibody-positive myasthenia gravis with rituximab.

We report on a 56-year-old woman with muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia with predominant bulbar symptoms and respiratory insufficiency. Conventional immunosuppression (prednisolone, azathioprine, mycophenolate mofetil) could not maintain the clinical improvement initially achieved by repeated plasma exchanges. Therefore, treatment with rituximab was initiated. After 2 months of rituximab treatment, remarkable clinical improvement correlating with a reduction of MuSK serum antibodies was seen. The patient continued to remain stable 12 months after initiation of therapy. This case report demonstrates that rituximab may be an effective and tolerable treatment in MuSK antibody-positive myasthenia gravis.

Adrenal Cortex Hormones↗
PubMed2006

Isolated bilateral blindness as the sole manifestation of transient ischaemic attacks.

PURPOSE: To explain the rare phenomenon of acute transient bilateral blindness without additional ophthalmological or neurological symptoms and signs. METHODS: Six patients with isolated bilateral visual loss lasting 1-15 mins and occurring simultaneously in both eyes were evaluated. Clinical observation, neuroimaging (CT, MRI, MR-angiography), extra- and transcranial Doppler and vascular risk factors assessment were performed. RESULTS: Cortical blindness due to bilateral occipital lobe transient ischaemic attacks (TIAs) was established as the most likely cause of acute transient visual loss in all patients. CONCLUSION: We suggest that in cases of transient bilateral blindness with sudden onset, appearing simultaneously in both visual fields, a bilateral ischaemia of the visual cortex should be suspected even if other neurological symptoms are lacking. Patients should be managed in the same way as patients with vertebrobasilar TIAs.

Acute Disease↗
PubMed2006

Ecto- and cytosolic 5'-nucleotidases in normal and AMP deaminase-deficient human skeletal muscle.

In skeletal muscle, adenosine monophosphate (AMP) is mainly deaminated by AMP deaminase. However, the C34T mutation in the AMPD1 gene severely reduces AMP deaminase activity. Alternatively, intracellular AMP is dephosphorylated to adenosine via cytosolic AMP 5'-nucleotidase (cN-I). In individuals with a homozygous C34T mutation, cN-I might be a more important pathway for AMP removal. We determined activities of AMP deaminase, cN-I, total cytosolic 5'-nucleotidase (total cN), ecto-5'-nucleotidase (ectoN) and whole homogenate 5'-nucleotidase activity in skeletal muscle biopsies from patients with different AMPD1 genotypes [homozygotes for C34T mutation (TT); heterozygotes for C34T mutation (CT); and homozygotes for wild type (CC): diseased controls CC; and normal controls CC]. AMP deaminase activity showed genotype-dependent differences. Total cN activity in normal controls accounted for 57+/-22% of whole homogenate 5'-nucleotidase activity and was not significantly different from the other groups. A weak inverse correlation was found between AMP deaminase and cN-I activities (r2=0.18, p<0.01). There were no significant differences between different groups in the activities of cN-I, whole homogenate 5'-nucleotidase and ectoN, or in cN-I expression on Western blots. No correlation for age, fibre type distribution and AMPD1 genotype was found for whole homogenate nucleotidase, total cN and cN-I using multiple linear regression analysis. There was no gender-specific difference in the activities of whole homogenate nucleotidase, total cN and cN-I. The results indicate no changes in the relative expression or catalytic behaviour of cN-I in AMP deaminase-deficient human skeletal muscle, but suggest that increased turnover of AMP by cN-I in working skeletal muscle is due to higher substrate availability of AMP.

5'-Nucleotidase↗
PubMed2005

Cyclic vertical deviation after ocular myositis and treatment by recession of the inferior rectus muscle.

BACKGROUND: Cyclic strabismus is a rare disorder in which strabismus and orthotropia regularly alternate over a period of mostly 48 h. It may occur spontaneously, upon squint surgery, or in association with lesions of the central nervous system. In most cases the deviations are convergent. METHODS: Clinical case report. RESULTS: A 34-year-old woman with bilateral recurrent ocular myositis for 2 years had developed cyclic vertical deviation 6 months after clinical remission. A hypotropia of the left eye alternated with an orthotropia, following a 48-h rhythm. Three months after recession of the inferior rectus muscle the alternating squint had disappeared. DISCUSSION: The aetiology of cyclic eye deviations, most of them occurring in a constant rhythm, is not known. The association with lesions of the central nervous system indicates a primary central dysregulation of a "biological clock". Their well-known occurrence, however, after squint surgery and, as in the present case, after orbital myositis, suggests that alteration of peripheral structures may contribute to a central dysregulation. Squint surgery seems to be the treatment of choice, even in rare cases with vertical deviations.

Adult↗
PubMed2005

Only subtle cognitive deficits in non-bulbar amyotrophic lateral sclerosis patients.

Neuropsychological investigations of amyotrophic sclerosis (ALS) patients revealed considerable discrepancies regarding neurocognitive functions. Some, but not all studies have suggested executive dysfunctioning and memory impairment, and there is a wide range of applied neuropsychological tests and results. In this study, we investigated the neuropsychological performance of 15 non-bulbar ALS patients, 14 patients with neuromuscular symptoms, and 15 healthy controls. To avoid confounding effects of motor disability, performance was assessed using exclusively motor-free tests of frontal lobe functioning (specific memory functions, conditional-associative learning, attention, and executive functions). ALS patients exhibited poorer performance in two conditions (semantic and alternating condition, respectively) of the Verbal Fluency Test, suggesting a subtle executive deficit. No deficits were found in tests of memory, conditional-associative learning, or attention. Assessed mood status was not related to neuropsychological performance. Verbal memory (CVLT) and verbal fluency (lexical condition) were positively associated with duration of disease. Our results support the view that there are only subtle cognitive deficits in ALS patients and we assume a possible effect of practice on cognitive tasks following reduced daily motor activity.

Aged↗
PubMed2005

[Hypokalemic thyrotoxic periodic paralysis (HTPP). Rare differential diagnosis in case of acute tetraparesis in Europe].

BACKGROUND: Differential diagnosis of acute tetraparesis includes paraplegia caused by trauma, ischemia, inflammation or tumor, Guillain-Barré syndrome, periodic paralysis, myasthenia gravis, and dissociative paralysis. CASE REPORT: The case of a 45-year-old man is reported who noticed weakness of both legs after heavy labor. In the evening he was unable to climb stairs, at night he noticed additional weakness in both arms and dyspnea. After transfer to the authors' department profound tetraparesis, tachycardia and slight dyspnea were found on examination. Cranial nerve examination was unremarkable. Deep tendon reflexes, however, were only slightly diminished. Laboratory work-up revealed hypokalemia (potassium 1.9 mmol/l) and hyperthyreosis. Elevated TRAK and TPO antibodies as well as sonography and scintigraphy of the thyroid gland gave evidence of Graves' disease. After intravenous administration of potassium tetraparesis resolved completely. CONCLUSION: Hypokalemic thyrotoxic periodic paralysis (HTPP), a subtype of hypokalemic paralysis, is unusual in Caucasians. In Asian men the disease is more common. The underlying mechanism is an extra-intracellular shift of potassium in the voluntary muscle cells. In contrast to hereditary autosomal dominant paralyses, a genetic defect is not known. Usually, symptoms of hyperthyreosis in HTPP are mild which can hamper the correct diagnosis.

Acute Disease↗
PubMed2005

Late-onset mitochondrial myopathy with dystrophic changes due to a G7497A mutation in the mitochondrial tRNA(Ser(UCN)) gene.

Mutations of mitochondrial tRNA genes are usually associated with multi-systemic disorders with onset of symptoms in childhood or early adulthood. Dystrophic myopathic changes are not typical features of these disorders. We report two siblings with a severe progressive myopathy of late onset without external ophthalmoplegia and without involvement of the central and peripheral nervous system. Muscle biopsy specimens showed severe myopathic changes similar to those found in muscular dystrophies. Molecular analysis revealed a G7497A mutation in the mitochondrial tRNA(Ser(UCN)) gene. In both patients, the proportion of mutated mitochondrial DNA in muscle was more than 97%. Mitochondrial disorder associated with the G7497A mutation has to be included into the differential diagnosis of severe progressive late-onset myopathy with histopathological dystrophic myopathic changes. Mitochondrial myopathy and high level of mutated mtDNA might be a characteristic of the G7497A tRNA(Ser(UCN)) mutation.

Adult↗
PubMed2005

Mitochondrial changes in skeletal muscle in amyotrophic lateral sclerosis and other neurogenic atrophies.

Previous findings suggested specific mitochondrial dysfunction in skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). To answer the question of whether the dysfunction is specific, we investigated the histochemical distribution of mitochondrial marker activities, the ratio of mitochondrial (mt) versus nuclear (n) DNA, and the activities of citrate synthase (CS) and respiratory chain enzymes in muscle biopsies of 24 patients with sporadic ALS. The data were compared with those in 23 patients with other neurogenic atrophies (NAs), and 21 healthy controls. Muscle histology revealed similar signs of focally diminished mitochondrial oxidation activity in muscle fibres in both diseased groups. There was only minimal decline of mt/nDNA ratios in ALS and NA patients in comparison with healthy controls. The specific activities of mitochondrial markers CS and succinate dehydrogenase were significantly increased in both ALS and NA patients. The specific activities of respiratory chain enzymes were not significantly different in all three groups. It is concluded that the histochemical, biochemical and molecular mitochondrial changes in muscle are not specific for ALS, but accompany other NAs as well.

Adult↗
PubMed2005

A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia.

Only four different mutations in the adenine nucleotide translocator 1 (ANT1) gene have been found in families with progressive external ophthalmoplegia (PEO). We report a novel heterozygous C to A transversion at nucleotide 269 in the ANT1 gene in a German family with PEO, predicted to convert a highly conserved alanine at codon 90 to aspartic acid. The mutation was identified in three siblings with PEO, one of them additionally suffered from schizoaffective disorder. Microsatellite analysis showed that the mutation was dominant and inherited from the mother who did not carry the mutation in blood, indicating germ-line mosaicism.

Adenine Nucleotide Translocator 1↗
PubMed2005

Effects of extramitochondrial ADP on permeability transition of mouse liver mitochondria.

Carboxyatractylate (CAT) and atractylate inhibit the mitochondrial adenine nucleotide translocator (ANT) and stimulate the opening of permeability transition pore (PTP). Following pretreatment of mouse liver mitochondria with 5 microM CAT and 75 microM Ca2+, the activity of PTP increased, but addition of 2 mM ADP inhibited the swelling of mitochondria. Extramitochondrial Ca2+ concentration measured with Calcium-Green 5N evidenced that 2 mM ADP did not remarkably decrease the free Ca2+ but the release of Ca2+ from loaded mitochondria was stopped effectively after addition of 2 mM ADP. CAT caused a remarkable decrease of the maximum amount of calcium ions, which can be accumulated by mitochondria. Addition of 2 mM ADP after 5 microM CAT did not change the respiration, but increased the mitochondrial capacity for Ca2+ at more than five times. Bongkrekic acid (BA) had a biphasic effect on PT. In the first minutes 5 microM BA increased the stability of mitochondrial membrane followed by a pronounced opening of PTP too. BA abolished the action about of 1 mM ADP, but was not able to induce swelling of mitochondria in the presence of 2 mM ADP. We conclude that the outer side of inner mitochondrial membrane has a low affinity sensor for ADP, modifying the activity of PTP. The pathophysiological importance of this process could be an endogenous prevention of PT at conditions of energetic depression.

Adenine Nucleotide Translocator 3↗
PubMed2005

Muscle carnitine palmitoyltransferase II deficiency: clinical and molecular genetic features and diagnostic aspects.

Muscle carnitine palmitoyltransferase (CPT) II deficiency is an autosomal recessive disorder of fatty acid oxidation characterized by attacks of myalgia and myoglobinuria. This review summarizes the clinical features of this disease, analyzing data of 28 patients with biochemically and genetically confirmed CPT II deficiency. The review shows that exercise-induced myalgia is the most frequent symptom, whereas myoglobinuria, known as the clinical hallmark, is missing in 21% of the patients. Typically, myalgia starts in childhood, whereas attacks with myoglobinuria mostly emerge in adolescence or early adulthood. However, there are also patients with only myalgia, patients with attacks triggered by factors other than exercise, and patients with late-onset disease. Molecular or biochemical analysis is necessary for diagnosis, since no myopathologic hallmark exists. For screening patients, analysis of not only the common S113L mutation but also the P50H and Q413fs-F448L mutations is recommended. The phenotype of muscle CPT II deficiency might be influenced by the underlying mutation, and patients with a truncating mutation on 1 allele might be affected more severely.

Adolescent↗